1. Field of the Invention
The present invention relates to animal feed compositions incorporating natamycin, an antifungal ingredient. The invention also relates to methods for producing and using such feed compositions.
2. Related Art
Mycotoxin is a well-known term that generally describes compounds produced by molds, or fungi, that produce toxic effects in other organisms. Acute diseases caused by mycotoxins are called mycotoxicoses. Outbreaks of mycotoxicoses have afflicted humans as well as domestic animals since antiquity.
A human disease known as Alimentary Toxic Aleukia was first detected in Russia during World War II, and it was caused by the human consumption of moldy grain, resulting in mortality rates as high as sixty percent (60%) in some of the affected areas. Diseases in domestic animals, such as horses, have also been recorded, caused by feeding them moldy hay. In the early 1950's in Japan, a condition known as "yellowed rice" was identified as the severe liver damage to animals ingesting fungus-contaminated rice. This disease is caused by a variety of Penicillium species. A discussion of the significance of mycotoxins is contained in Bullerman's, "Significance of Mycotoxins to Food Safety and Human Health", Journal of Food Protection, Volume 42, page 65, 1979.
Other mycotoxicoses have been reported in sheep in New Zealand, resulting in severe liver damage and skin disorders. Further outbreaks produced by moldy feed have been reported in horses, cattle, poultry, and swine. In England, in 1960, a severe toxic outbreak of a mycotoxicosis known as "Turkey X Disease" was traced to moldy ground meal that had been heavily infested with a common mold Aspergillus flavus. Analysis of the mycotoxin in this feed resulted in the discovery of several compounds that were named aflatoxins and which are now known to be carcinogenic.
Thus, it has been recognized that fungus growth in animal feedstuffs may result in mycotoxicoses in valuable livestock. Furthermore, even if the fungus in the feedstuff is killed, fungal toxins that are present will remain, representing a continuing hazard. Several authorities have suggested various prophylactic steps. For example, recognizing the importance of feed as a source of toxigenic fungi, one author found it imperative that feeds and feed handling equipment be kept dry to prevent fungal growth and toxin formation (Lovett, Journal of Agriculture and Food Chemistry, Volume 20, 1972). This approach, while helpful, appears to be inadequate, given the natural moisture content that is present in all animal feeds.
Another approach to the control of mycotoxins is through the use of antifungal or antimycotic compounds. Such agents are chemicals that prevent or interfere with mold growth and also, in some instances, with the production of the mycotoxins themselves. For example, U.S. Pat. No. 4,126,701 discloses an animal and poultry feed which contains a medicinal agent, gentian violet, that is a selective fungicidal mold inhibitor for Candida Albicans. A suggested feed composition is formulated by adding a premix concentrate containing gentian violet along with medically inert ingredients to a conventional feed composition. U.S. Pat. No. 3,916,027 discloses a related premix concentrate also utilizing gentian violet as a method of treating Candida albicans infections in poultry.
Fungal infections and mycotoxins are not limited to domestic animals nor only transmitted through contaminated feedstuffs. As noted above, mycotoxicoses have been reported in human populations. Fungi produce a variety of human clinical pathologies through infections as well as through consumption of fungus-contaminated foods. Certain antifungal agents have been used to treat or prevent the growth of fungus both clinically and on foods.
One such antifungal agent is natamycin, also known as pimaricin or tennectin. This compound was isolated in the late 1950's from the fermentation broth of a culture of Streptomyces natalensis. (See Struyk et al., Antibiotics Annual, 1957-1958, page 878.) This organism was discovered in a soil sample taken from near Pietermaritzburg in South Africa. Natamycin is also produced by Streptomyces chattanoogensis.
Natamycin is a creamy white, odorless, tasteless, practically insoluble crystalline amphoteric powder. It belongs to the polyene macrolide or macrocyclic lactone group of compounds. (See generally, Clark et al. "Pimaricin, A New Food Fungistat", Microbial Inhibitors in Food, 4th International Symposium on Food Microbiology 1964 at the Swedish Institute for Food Preservation Research.) In low concentrations, natamycin is a potent inhibitor of fungal microorganisms. It is reported to have been tested in vitro on over 500 fungal organisms and with very positive effects.
Natamycin is relatively stable when in a dry state or when mixed with dry diluents. However, the molecule is sensitive to ultraviolet light, oxygen, or extreme pH values. It is relatively insoluble in water in which its solubility is of the order 0.005-0.010 weight/weight percent. Additionally, even in solution, natamycin is rather unstable. Aqueous solutions of 16 mcg/ml of natamycin became microbiologically inactive after 24 hour exposure to light. Inactivation of natamycin by light, peroxides or oxygen proceeds at the fastest rate in solution or suspension. Natamycin is also sensitive to heavy metals, and it may lose up to 75% of its effectivity in 4-5 hours in their presence.
Natamycin has been used to treat several human clinical fungal infections, such as Candidiasis and Trichomoniasis. As reported in the British National Formulary, natamycin is sold under the trade name "Pimafucin.RTM." produced by Brocades in oral suspension, suspension for inhalation, cream and vaginal tablet formulations. Natamycin has also been used for various epidermal fungal infections such as corneal ulcers.
Natamycin has also been of interest in the treatment of food products because it is highly active against yeasts and molds, as opposed to bacterial (see Morris and Hart, "Pimaricin--What is It?", Culture Dairy Products Journal, Volume 13, page 22, 1978.) Reportedly, natamycin has been applied to food products in several ways. It has been added in dry form to liquids, slurries, pastes and semisolids when adequate mixing can be accomplished, or the pure natamycin can be mixed with one or more of the dry ingredients and then added to a given food product. Solid foods requiring surface protection can be dipped, misted, fogged or dusted with a solution or suspension of natamycin. Additionally, it has been suggested that protection from yeast and molds may be achieved in solid food by incorporating natamycin homogeneously into the food itself. (See, Clark et al. cited above.)
Natamycin has also been used to retard spoilage of dressed poultry, to protect cottage cheese, and has been widely used in the dip-treatment of cheeses to coat them with the fungicide which is absorbed slightly, and dries to form a solid, surface coating. Various other reports suggest that natamycin is effective in the treatment of fresh berries, tomatoes, strawberries and raspberries. These reports indicate that natamycin has an antiyeast activity when added to wines, and various fruit juices, such as apple juice or orange juice. (See, Morris and Hart, and Clark, cited above.) Natamycin is also used on meat products such as sausage.